The myocardial matrix and the development and progression of ventricular remodeling

Sackner‐Bernstein, Jonathan

doi:10.1007/s11886-000-0007-4

Cited by 35 publications

(23 citation statements)

References 90 publications

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“…Mechanical stretch, a hallmark of arterial hypertension that leads to vessel wall remodeling and induces formation of reactive oxygen species by NAD(P)H oxidase, increases the expression and activity of MMPs, and reactive oxygen species contribute to vascular remodeling associated with arterial hypertension through MMP activation (41). Given that the extracellular matrix not only provides a supportive scaffold for myocytes and maintains the structural integrity of the heart but also cooperates with myocytes in activation conduction, changes in extracellular matrix components in the atrium have been considered likely to contribute to the development of sustained AF (42,43). Remodeling of the atrial extracellular matrix, manifested by selective downregulation of TIMP2 expression and up-regulation of MMP2 expression, has been associated with the development of sustained AF (43).…”

Section: Discussionmentioning

confidence: 99%

Genetic factors for lone atrial fibrillation

Kato

Oguri²,

Hibino³

et al. 2007

Int J Mol Med

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Abstract. Atrial fibrillation (AF) may result from an electric conduction disturbance, increased hemodynamic stress, ischemia, inflammation, or remodeling in atria. Although genetic epidemiological studies have identified several genetic variants as risk factors for AF, the genetic determinants of this condition remain largely unknown. The purpose of the present study was to identify gene polymorphisms that confer susceptibility to lone AF. The study population comprised 1069 unrelated Japanese individuals, including 196 subjects with chronic lone AF and 873 controls. The genotypes for 40 polymorphisms of 32 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and hypercholesterolemia as well as a stepwise forward selection procedure revealed that the -1306C➝T polymorphism of the matrix metalloproteinase 2 gene (MMP2) and the -592A➝C polymorphism of the interleukin 10 gene (IL10) were significantly (false discovery rate of <0.05) associated with the prevalence of AF. The T allele of the MMP2 polymorphism and the C allele of the IL10 polymorphism were a risk factor for and protective factor against AF, respectively. Determination of the genotypes for these polymorphisms may thus prove informative for assessment of the genetic component of AF.

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Section: Discussionmentioning

confidence: 99%

Genetic factors for lone atrial fibrillation

Kato

Oguri²,

Hibino³

et al. 2007

Int J Mol Med

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“…Specifically, in both human and animal studies, it has been reported that alterations in the collagen interface, both in structure and composition, occur within the LV myocardium, which, in turn, may influence LV geometry. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] The myocardial ECM contains a fibrillar collagen network, a basement membrane, proteoglycans and glycosaminoglycans, and bioactive signaling molecules. The myocardial fibrillar collagens, such as collagen types I and III, ensure structural integrity of the adjoining myocytes, provide the means by which myocyte shortening is translated into overall LV pump function, and are essential for maintaining alignment of the myofibrils within the myocyte through a collagen-integrincytoskeletal myofibril relation.…”

mentioning

confidence: 99%

“…The identification and understanding of the enzyme systems responsible for ECM degradation within the myocardium has particular relevance in the progression of CHF. The purpose of the present review is 3-fold: (1) to present a brief overview of a proteolytic system within the myocardium that likely contributes to ECM remodeling, ie, the matrix metalloproteinases (MMPs); (2) to examine the results from basic studies that have used pharmacological and genetic strategies to provide a cause-and-effect relationship with respect to MMP activation and the LV remodeling process; and (3) to demonstrate how this system is upregulated or, arguably, dysregulated in patients with CHF.…”

mentioning

confidence: 99%

Matrix Metalloproteinases

Spinale

2002

Circulation Research

641

260

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Abstract-Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes responsible for myocardial extracellular protein degradation. Several MMP species identified within the human myocardium may be dysregulated in congestive heart failure (CHF). For example, MMPs that are expressed at very low levels in normal myocardium, such as collagenase-3 (MMP-13) and the membrane-type-1 MMPs, are substantially upregulated in CHF. However, MMP species are not uniformly increased in patients with end-stage CHF, suggesting that a specific portfolio of MMPs are expressed in the failing myocardium. With the use of animal models of CHF, a mechanistic relationship has been demonstrated with respect to myocardial MMP expression and the left ventricular (LV) remodeling process. The tissue inhibitors of the MMPs (TIMPs) are locally synthesized proteins that bind to active MMPs and thereby regulate net proteolytic activity. However, there does not appear to be a concomitant increase in myocardial TIMPs during the LV remodeling process and progression to CHF. This disparity between MMP and TIMP levels favors a persistent MMP activation state within the myocardium and likely contributes to the LV remodeling process in the setting of developing CHF. The elucidation of upstream signaling mechanisms that contribute to the selective induction of MMP species within the myocardium as well as strategies to normalize the balance between MMPs and TIMPs may yield some therapeutic strategies by which to control myocardial extracellular remodeling and thereby slow the progression of the CHF process. (Circ Res. 2002;90:520-530.)Key Words: myocardial remodeling Ⅲ heart failure Ⅲ matrix metalloproteinases Ⅲ matrix metalloproteinase inhibitors

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“…Applying UTI may make inside diameter of ventricular smaller, while the fractional shortening of left ventricular increases. It was indicated that UTI may inhibit ventricular remodeling after heart failure, and the effect is most obvious under the condition of high dosage [9][10][11]. (ii) Inhibiting myocardial interstitial fibrosis.…”

Section: Discussionmentioning

confidence: 99%

The protection effects of different dosages of ulinastatin on myocardial

Ling¹,

Sun²

2016

Integr Mol Med

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The aim is to explore the protection effect of ulinastatin (UTI) on myocardial in different dosages and its mechanism. From May to August 2014, in the animal laboratory of the 309th hospital of PLA, the experiment was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals for the National Institutes of Health. The animal protocol was approved by the Institutional Animal Care Committee of the 309th Hospital of PLA (Permit Number: 13-269). 120 SD rats were randomly divided into control group (treated with normal saline), UTI low-dose group (30000 IU/kg), UTI moderate-dose group (60000 IU/kg) and high-dose group (90000 IU/kg). All rats were treated with UTI for 2 weeks via vein. Then left ventricular end diastolic diameter (LVEDD), left ventricular endsystolic dimension (LVESD) and left ventricular ejection fraction (LVEF) were employed to evaluate heart function. Hyp determination with chloramine-T oxidation method was employed to detect the myocardial fibrosis degree, while brain natriuretic peptide (BNP) was used to assess heart function. By comparison among groups, the results of the high-dose group were better than that of any other group in LVEDD, LVESD, LVEF, BNP content, as well as in heart function.It is better for myocardial protection with high-dose of ulinastatin, the possible mechanism is relevant to inhibit myocardial interstitial fibrosis and ventricular remodeling.

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The myocardial matrix and the development and progression of ventricular remodeling

Cited by 35 publications

References 90 publications

Genetic factors for lone atrial fibrillation

Genetic factors for lone atrial fibrillation

Matrix Metalloproteinases

The protection effects of different dosages of ulinastatin on myocardial

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